1. Field of the Invention
The present invention relates to a DNA amplification device suitable for use when amplifying DNA (deoxyribonucleic acid).
2. Description of the Relevant Art
In general, the PCR method (polymerase chain reaction method) is known as a method for DNA amplification. The PCR method is a method where primers, an enzyme(s) and deoxyribonucleoside triphosphate, reacted with a DNA sample, are added to the DNA sample, whereupon the reaction solution is heated (or cooled down) by a heat cycle changed according to a pre-determined temperature pattern, and concurrently, where the sequential repetition of the heat cycle results in the amplification of the DNA.
Another DNA amplification device for realizing the PCR method is also known, for example, in the publication of Japanese Laid-Open Patent Application No. 2003-174863, which discloses a DNA amplification device equipped with a heating & cooling means established on an inorganic substrate, multiple reaction cells formed in a lattice pattern on the heating & cooling means, on the upper surfaces of which reaction cells is established a temperature measuring means, where electric heat conversion devices, in which a P-type peltiert element and an N-type peltiert element are regarded as one pair, are used as a heating & cooling means, and concurrently, where they are arranged in a lattice pattern at positions opposing the reaction cells.
For the cells (reaction cells) established in the DNA amplification device, multiple concave parts are normally formed & arranged at pre-determined intervals on the upper surface of a block board using a silicone wafer material or an aluminum material, the concave parts being directly constructed as cells (reaction cells), or in a construction in which the cells (tubes) are filled into the concave parts. With such construction, the block board where the cell group is formed functions as a processing block, with the bottom surface of the block board being heated or cooled down from the heating & cooling side of a thermo-module 3.
In the meantime, the heating & cooling means (thermo-module) where the peltiert elements are used is normally configured as shown in FIG. 15. The thermo-module 3 shown in the diagram is constructed with a structure where multiple peltiert elements d . . . are connected [with each other] and regarded as a series aggregate P, the series aggregate P being interposed between a pair of substrates 51 & 52. In this case, multiple electrodes e . . . are established at a constant interval on the facing surfaces (internal surfaces) of each of the substrates 51 & 52, the end of each peltiert element d . . . generally being joined to each electrode e . . . using solder. With this construction, if the electrification direction to the series aggregate P is switched to the forward direction or reverse direction, the thermo-module 3 can be operated for heating or for cooling. At this time, during heating, the heat radiation side (opposite the heating & cooling side) of the thermo-module 3 is cooled down. At the same time, when cooling, the heat radiation side of the thermo-module 3 is heated, so an aluminum heat sink 53 is attached to the heat radiation side, heat radiation (or heat absorption) being performed via the heat sink 53.
However, in the case of using a processing block provided with this cell group for the DNA amplification device, there are problems that the following nonconformities may occur:
In this type of DNA amplification device, for pre-determined heating & cooling performance to a reaction solution, prompt temperature-rising performance or temperature-fall performance is especially required. However, this DNA amplification device cannot sufficiently respond to this required performance. In the DNA amplification device, as shown in FIG. 14, heating is performed according to a heat cycle where, after heating is performed at 94 [° C.] for T1 [sec], separate heating is performed at 50 [° C.] for T2 [sec], and heating is additionally performed at 72 [° C.] for T3 [sec]. At the same time, the heat cycle is normally repeated dozens of times. In this case, in a temperature pattern F shown in the chart, a temperature-falling period of time Td and temperature-rising periods of time Tf and Ts, in addition, another temperature-fall period of time Th to lower the temperature from 94 [° C.] to 4 [° C.] when storing a reaction solution within the cells at a low temperature must be as short as possible. Because the block board, where the heat capacity and the coefficient of thermal expansion are great, and which lowers thermal conductivity, intervenes between the cells and the thermo-module 3, prompt temperature-rising & temperature-falling controls cannot be realized. Without prompt temperature-rising & temperature-falling controls, there is not only no realization of flexible and accurate temperature control, but also in the longer duration in one process, it will lead the reduction of process efficiency and the reduction of power saving properties.
Further, the repetitive operation of the heat cycle may cause creeping at the soldered joints between the electrodes e . . . and the peltiert elements d . . . due to the modulus of longitudinal elasticity, the coefficient of the thermal expansion and a difference in thermal expansion, depending upon the temperature in the substrates 51 & 52, the electrodes e . . . and the peltiert elements d . . . , which creeping causes a thermal stress fraction, such as poor contact or breaking of wire, to the soldered joints. In particular, the generated direction of creeping is opposite between the heat radiation side (the substrate 52 side) and the heating & cooling side (the substrate 51 side). In other words, as shown by the outline arrows in FIG. 15, when creep is generated in the contraction direction on either the heat radiation side or the heating & cooling side, since separate creeping will be generated in the expansion direction on the other side, the thermal stress will also be substantially doubled.
In the meantime, in order to inhibit the generation of creeping, it is effective to reduce the temperature variation at the soldered joints as much as possible. For this purpose, it is necessary to enlarge the volume of the heat sink 53 and to reduce the thermal resistance. However, there is a limit to enlargement of the volume of the heat sink 53. Normally, the thickness of a foundation 53b of the heat sink 53 is established at 10-15 [mm] from the viewpoint of reducing the thermal resistance and enhancing the rigidity, at the same time, preventing a warp (curvature) of the foundation 53b. Even in this case, the temperature variation of the soldered joints is approximately 5-10 [° C.], and the temperature variation at the soldered joints cannot be sufficiently inhibited, and the At the same time, it causes great enlargement of the entire thermo-module 3. In addition, in the case that the multiple thermo-modules 3 are scattered and arranged, the temperature greatly varies between each thermo-module 3, so even DND amplification to all cells cannot be performed.